OBJECTIVE: Vascular groin incision complications contribute significantly to patients' morbidity and rising health care costs. Negative pressure therapy over the closed incision decreases the infection rate in cardiac and orthopedic procedures. This study prospectively evaluated negative pressure therapy as a means to decrease wound complications and associated health care costs. METHODS: This was a randomized, prospective, single-institution study of 119 femoral incisions closed primarily after elective vascular surgery including both inflow (eg, aortofemoral) and outflow (eg, femoral-popliteal bypass) procedures. Incisions were categorized as high risk for wound complications on the basis of body mass index >30 kg/m2, pannus, reoperation, prosthetic graft, poor nutrition, immunosuppression, or hemoglobin A1c >8% and randomized 1:1 to standard gauze (n = 60) dressing vs negative pressure therapy (Prevena [Acelity, San Antonio, Tex], n = 59). Wound complication rate, length of stay (LOS), reoperation, readmission, and variable hospital costs were determined during 30 days. Statistical analysis was performed using χ2 test along with a two-sample unpaired t-test for continuous variables. RESULTS: There were no significant demographic differences (age, sex, risk factors for wound complication) between the two high-risk groups. In low-risk controls, the major wound complication rate was 4.8% (involving one infection in 21 incisions), resulting in a 3.8-day LOS, 4.8% reoperation, 4.8% readmission rate, and $17,599 in average variable cost. For high-risk controls, there was a significant increase in major wound complications to 25% (including all 12 infections in 60 incisions), LOS (10.6 days), reoperation (18.3%), readmission (16.7%), and costs ($36,537). Finally, negative pressure therapy significantly reduced major wound complications to 8.5% (including five of six infections in 59 incisions; P < .001), reoperation (8.5%; P < .05), and readmission (6.8%; P < .04) but not LOS (10.6 days). The average variable cost was reduced ($30,492), yielding an average savings of $6045 per patient (P = .11). CONCLUSIONS: This study suggests that negative pressure therapy significantly reduces the major wound complication, reoperation, and readmission rates for patients at high risk for groin wound complications. Furthermore, this therapy may lead to a reduction in hospital costs. Negative pressure therapy for all groin incisions considered at high risk for wound complications is recommended.